Pediatric Lung and Heart-Lung Transplants in Pulmonary Vascular Diseases

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In this study published in JHLT, the focus theme is on Pediatric Lung and Heart-Lung Transplants related to Pulmonary Vascular Diseases (PVD). The analysis includes Kaplan-Meier Survival Analyses, recipient characteristics, distribution of diagnoses, and more from the years 1992 to 2018. The data sheds light on the trends and outcomes in pediatric patients undergoing these transplants.

  • Pediatric
  • Lung Transplants
  • Heart-Lung Transplants
  • Pulmonary Vascular Diseases
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  1. FOCUS THEME: PULMONARY VASCULAR DISEASES (PVD) Pediatric Lung and Heart-Lung 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  2. Table of Contents Number of Deceased Donor Transplants and Recipient Characteristics by Transplant Year/Era: slides 3-15 Kaplan-Meier Survival Analyses: slides 16-31 Survival within 12 months: slides 16-23 Survival within 5 years conditional on survival to 1 year: slides 24-30 Freedom from BOS/CLAD within 5 years conditional on survival to discharge: slides 31-33 Multivariable Analyses: slides 34-39 Cox model for mortality within 12 months: slides 34-37 Cox model for mortality within 5 years conditional on survival to 1 year: slides 38-39 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  3. Number of Deceased Donor Transplants and Recipient Characteristics by Transplant Era/Year 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  4. Pediatric Lung and Heart-Lung Transplants Diagnosis Distribution (Transplants: January 1992 June 2018) Jan 1992-Dec 2000 (N = 855) Jan 2001-Dec 2009 (N = 952) Jan 2010-Jun 2018 (N = 970) P-value Diagnosis - Pulmonary vascular disease (PVD) 247 (30.8%) 162 (17.9%) 194 (20.5%) - Idiopathic pulmonary arterial hypertension (IPAH) 107 (13.3%) 105 (11.6%) 135 (14.3%) - Pulmonary hypertension (PH-not IPAH) 140 (17.5%) 57 (6.3%) 59 (6.2%) <0.0001 - Cystic Fibrosis (CF) 391 (48.8%) 504 (55.6%) 482 (51.0%) - Obstructive bronchiolitis (OB non-Retransplant) 14 (1.7%) 51 (5.6%) 49 (5.2%) - Interstitial lung disease (ILD not IIP) 19 (2.4%) 44 (4.9%) 54 (5.7%) - Retransplant 51 (6.4%) 56 (6.2%) 49 (5.2%) - Other 80 (10.0%) 89 (9.8%) 118 (12.5%) 2022 Continuous factors are expressed as median (5th 95th percentiles) Summary statistics included transplants with non-missing data JHLT. 2022 Oct; 41(10): 1335-1375

  5. Pediatric Lung and Heart Lung Transplants with PVD Recipient Characteristics (Transplants: January 1992 June 2018) Jan 1992-Dec 2000 (N = 247) Jan 2001-Dec 2009 (N = 162) Jan 2010-Jun 2018 (N = 194) P-value Geographic Location - Europe - North America - Other Age (years) (continuous) Age (categorical) 28.7% 67.6% 3.6% 29.0% 63.6% 7.4% 46.4% 43.8% 9.8% <0.0001 11.0 (0.0 - 17.0) 13.0 (0.0 - 17.0) 13.0 (0.0 - 17.0) 0.071 - <1 years - 1-5 years - 6-10 years - 11-17 years Male 10.9% 23.1% 14.6% 51.4% 45.7% 9.9% 16.7% 11.7% 61.7% 41.4% 5.7% 22.7% 12.9% 58.8% 43.8% 0.206 0.681 Weight (kg) Height (cm) BMI (kg/m ) 53.0 (41.0 - 78.0) 163.0 (148.0 - 180.0) 19.7 (15.6 - 27.7) 54.7 (40.9 - 82.0) 162.0 (149.9 - 181.3) 19.9 (15.9 - 27.8) 53.0 (41.0 - 78.6) 162.0 (146.0 - 180.0) 20.1 (15.9 - 31.2) 0.664 0.836 0.444 2022 Summary statistics included transplants with non-missing data Continuous factors are expressed as median (5th 95th percentiles) JHLT. 2022 Oct; 41(10): 1335-1375

  6. Pediatric Lung and Heart Lung Transplants with PVD Recipient Characteristics (Transplants: January 1992 June 2018) Jan 1992-Dec 2000 (N = 247) Jan 2001-Dec 2009 (N = 162) Jan 2010-Jun 2018 (N = 194) P-value ABO blood type - A 44.5% 46.9% 35.6% - AB 4.1% 5.6% 6.7% 0.368 - B 9.8% 9.3% 11.9% - O 41.6% 38.3% 45.9% Donor-recipient sex match 27.5% 28.6% 33.0% - Female-Female 15.4% 16.8% 25.3% - Female-Male 0.022 26.7% 29.8% 23.2% - Male-Female - Male-Male 30.4% 24.8% 18.6% Transplant procedure - Lung 40.1% 57.4% 80.9% <0.0001 - Heart-Lung 59.9% 42.6% 19.1% 2022 Summary statistics included transplants with non-missing data JHLT. 2022 Oct; 41(10): 1335-1375

  7. Pediatric Lung and Heart Lung Transplants with PVD Recipient Characteristics (Transplants: January 1992 June 2018) January 1992-Dec 2000 (N = 247) 7.1% January 2001-Dec 2009 (N = 162) 5.2% January 2010-Jun 2018 (N = 194) 16.4% P-value PRA 20% 0.0375 PRA 80% 2.1% 3.9% 0.0% 0.2684 Previous cardiothoracic surgery 34.9%1 35.8% 33.3% 0.9348 Hospitalized 41.4% 45.5% 47.7% 0.599 Ventilator use 19.5% 19.6% 19.3% 0.9985 ECMO use 4.3% 5.6% 13.3% 0.0349 CMV antibody positive 17.8% 30.5% 26.8% 0.0588 EBV antibody positive 50.0% 2 52.1% 45.6% 0.6695 Hepatitis B antibody positive 2.0% 1 5.0% 2.6% 0.493 Hepatitis C antibody positive 2.0%1 2.2% 0.0% 0.3778 Summary statistics included transplants with non-missing data 2022 1 Based on Apr 1994 Dec 2000 transplants JHLT. 2022 Oct; 41(10): 1335-1375 2 Based on Oct 1999 Dec 2000 transplants

  8. Pediatric Lung and Heart Lung Transplants with PVD Recipient Characteristics (Transplants: January 1992 June 2018) Jan 1992-Dec 2000 (N = 247) Jan 2001-Dec 2009 (N = 162) Jan 2010-Jun 2018 (N = 194) P-value Bilirubin (mg/dl) 0.7 (0.3 - 2.0) 1 0.5 (0.2 - 1.7) 0.4 (0.2 - 1.2) 0.0007 Creatinine(mg/dl) 0.5 (0.2 - 1.1) 1 0.6 (0.2 - 1.1) 0.4 (0.1 - 1.0) 0.0014 GFR (mL/min/1.73m2)* 88.8 (57.1 - 119.1) 1 89.3 (55.9 - 156.4) 96.9 (59.4 - 163.1) 0.082 PCW mean (mmHg) 13.5 (4.0 - 35.0) 1 12.0 (4.0 - 32.0) 11.0 (6.0 - 21.0) 0.278 PA mean (mmHg) 58.0 (19.5 - 79.5) 1 60.5 (16.0 - 80.0) 59.0 (13.0 - 80.0) 0.6798 PVR (Wood units) 17.2 (3.6 - 37.3) 1 13.3 (0.8 - 27.7) 8.9 (0.4 - 31.9) 0.4378 FEV1% predicted 47.0 (26.0 - 69.0) 72.0 (47.0 - 99.0) 76.0 (42.0 - 99.0) 0.0047 FVC% predicted 53.0 (30.0 - 86.0) 78.0 (50.0 - 104.0) 80.0 (50.0 - 102.0) 0.0286 Summary statistics included transplants with non-missing data Continuous factors are expressed as median (5th 95th percentiles) 2022 * GFR was estimated using the modified Schwartz formula JHLT. 2022 Oct; 41(10): 1335-1375 1 Based on Apr 1994 Dec 2000 transplants

  9. Pediatric Lung and Heart-Lung Transplants Diagnosis Distribution by Location and Era (Transplants: January 1992 June 2018) 100% Other 80% Retransplant % of transplants ILD not IIP 60% OB (non-Retx) 40% CF PH-not IPAH 20% IPAH 0% 1992-2000 2001-2009 2010-2018 Europe 1992-2000 2001-2009 2010-2018 North America 1992-2000 2001-2009 2010-2018 Other 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  10. Pediatric Lung and Heart Lung Transplants with PVD Median Recipient BMI (Transplants: January 1992 June 2018) Median Recipient Age (Transplants: January 1992 June 2018) Overall 30 20 28 18 26 16 24 14 Median BMI (kg/m2) Median Age (years) 22 12 20 10 18 8 6 16 4 14 2 12 0 10 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  11. Pediatric Lung and Heart-Lung Transplants with PVD Recipient Sex Distribution by Location and Era (Transplants: January 1992 June 2018) Female Male 100% 80% % of transplants 60% 40% 20% 0% 1992-2000 2001-2009 Europe 2010-2018 1992-2000 2001-2009 North America 2010-2018 1992-2000 2001-2009 Other 2010-2018 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  12. Pediatric Lung and Heart Lung Transplants with PVD Donor-Recipient Sex Distribution by Location and Era (Transplants: January 1992 June 2018) Female-Female Female-Male Male-Female Male-Male 100% 80% % of transplants 60% 40% 20% 0% 1992-2000 2001-2009 Europe 2010-2018 1992-2000 2001-2009 North America 2010-2018 1992-2000 2001-2009 Other 2010-2018 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  13. Pediatric Lung and Heart Lung Transplants with PVD Recipient ABO Blood Type Distribution by Location and Era (Transplants: January 1992 June 2018) A AB B O 100% 80% % of transplants 60% 40% 20% 0% 1992-2000 2001-2009 Europe 2010-2018 1992-2000 2001-2009 North America 2010-2018 1992-2000 2001-2009 Other 2010-2018 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  14. Pediatric Lung and Heart Lung Transplants with PVD Cause of Death (Deaths: January 1992 June 2018) 1 Year (N = 130) 1 Year - 5 Years (N = 101) >5 Years (N = 51) Cause of Death OB/BOS 5 (3.8%) 45 (44.6%) 21 (41.2%) Acute Rejection 7 (5.4%) 2 (2.0%) 1 (2.0%) Malignancy 2 (1.5%) 3 (3.0%) 1 (2.0%) Infection 21 (16.2%) 11 (10.9%) 3 (5.9%) Graft Failure 35 (26.9%) 24 (23.8%) 15 (29.4%) Cardiovascular 19 (14.6%) 3 (3.0%) 4 (7.8%) Multiple Organ Failure 15 (11.5%) 5 (5.0%) 2 (3.9%) Other 26 (20.0%) 8 (7.9%) 4 (7.8%) 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  15. Primary Pediatric Lung and Heart Lung Transplants with PVD Cumulative Incidence of Retransplant (Transplants: January 1995 June 2017) 20% 16% 12% Incidence 8% 4% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  16. Survival Analyses Kaplan-Meier Survival Within 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  17. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 12 Months by Era (Transplants: January 2000 - June 2017) 2000-2008 2009-2017 100 75 Survival (%) 50 p = 0.50 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  18. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 12 Months by Era and Location (Transplants: January 2000 - June 2017) 2000-2008 2009-2017 100 100 75 75 Survival (%) Survival (%) 50 50 p = 0.70 p = 0.59 25 25 0 0 0 1 2 3 4 5 Months Europe 6 7 8 9 10 11 12 0 1 2 3 4 5 6 7 8 9 10 11 12 Months North America 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  19. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 12 Months by Recipient Age (Transplants: January 2000 - June 2017) 0-5 Years 6-10 Years 11-17 Years 100 75 Survival (%) 50 No pairwise comparisons were significant at p < 0.05 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  20. Pediatric Lung and Heart-Lung Transplants Kaplan-Meier Survival within 12 Months by Diagnosis (Transplants: January 2000 - June 2017) PVD CF Other 100 75 Survival (%) 50 No pairwise comparisons were significant at p < 0.05 except PVD vs. CF 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  21. Pediatric Lung and Heart-Lung Transplants Kaplan-Meier Survival within 12 Months by Diagnosis (Transplants: January 2000 - June 2017) IPAH PH-not IPAH CF Other 100 75 Survival (%) 50 25 No pairwise comparisons were significant at p < 0.05 except PH-not IPAH vs. CF and PH-not IPAH vs. Other 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  22. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 12 Months by Recipient eGFR* (Transplants: January 2000 - June 2017) <90 (mL/min/1.73 m ) 90 (mL/min/1.73 m ) 100 75 Survival (%) 50 p = 0.30 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months 2022 *GFR was estimated using the modified Schwartz formula JHLT. 2022 Oct; 41(10): 1335-1375

  23. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 12 Months by Procedure Type (Transplants: January 2000 - June 2017) Lung (N=249) Heart-Lung (N=109) 100 75 Survival (%) 50 p = 0.28 25 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  24. Survival Analyses Kaplan-Meier Survival Within 5 Years Conditional on Survival to Discharge 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  25. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 5 Years Conditional on Survival to 1 Year By Era (Transplants: January 1996 - June 2013) 1996-2004 2005-2013 100 75 Survival (%) 50 p = 0.15 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  26. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 5 Years Conditional on Survival to 1 Year By Recipient Age (Transplants: January 1996 - June 2013) 0-5 Years 6-10 Years 11-17 Years 100 75 Survival (%) 50 No pairwise comparisons were significant at p < 0.05 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  27. Pediatric Lung and Heart Lung Transplants Kaplan-Meier Survival within 5 Years Conditional on Survival to 1 Year By Diagnosis (Transplants: January 1996 June 2013) PVD CF Other 100 75 Survival (%) 50 No pairwise comparisons were significant at p < 0.05 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  28. Pediatric Lung and Heart Lung Transplants Kaplan-Meier Survival within 5 Years Conditional on Survival to 1 Year By Diagnosis (Transplants: January 1996 June 2013) IPAH PH-not IPAH CF Other 100 75 Survival (%) 50 No pairwise comparisons were significant at p < 0.05 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  29. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 5 Years Conditional on Survival to 1 Year by Recipient eGFR* (Transplants: January 1996 - June 2013) <90 (mL/min/1.73 m 90 (mL/min/1.73 m 100 75 Survival (%) 50 p = 0.71 25 0 0 1 2 3 4 5 Years 2022 *GFR was estimated using the modified Schwartz formula JHLT. 2022 Oct; 41(10): 1335-1375

  30. Pediatric Lung and Heart Lung Transplants with PVD Kaplan-Meier Survival within 5 Years Conditional on Survival to 1 Year by Procedure Type (Transplants: January 1996 - June 2013) Lung Heart-Lung 100 75 Survival (%) 50 p = 0.08 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  31. Survival Analyses Kaplan-Meier Freedom from BOS Conditional on Survival to Discharge 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  32. Pediatric Lung and Heart Lung Transplants with PVD Freedom from BOS/CLAD Conditional on Survival to Discharge By Era (Transplants: January 1996 - June 2013) 1996-2004 2005-2013 100 Freedom from BOS /CLAD (%) 75 50 p = 0.62 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  33. Pediatric Lung and Heart Lung Transplants with PVD Freedom from BOS/CLAD Conditional on Survival to Discharge By Recipient Age (Transplants: January 1996 - June 2013) 0-5 Years 6-10 Years 11-17 Years 100 Freedom from BOS/CLAD (%) 75 50 No pairwise comparisons were significant at p < 0.05 = 25 0 0 1 2 3 4 5 Years 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  34. Multivariable Cox Analyses Mortality within 12 Months 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  35. Pediatric Lung and Heart-Lung Recipients with PVD (1990-6/2017) Statistically Significant Categorical Risk Factors For 1-Year Mortality with 95% Confidence Limits 2022 (N = 637) JHLT. 2022 Oct; 41(10): 1335-1375

  36. Pediatric Lung and Heart-Lung Recipients with PVD (1990-6/2017) Statistically Significant Continuous Risk Factors For 1-Year Mortality Continuous Factors (see figures) Recipient eGFR (mL/min/1.73 m ) 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  37. Pediatric Lung and Heart-Lung Recipients with PVD (1990-6/2017) Statistically Significant Risk Factors For 1-Year Mortality with 95% Confidence Limits Recipient eGFR (mL/min/1.73 m ) 5.0 Hazard Ratio of 1-Year Mortality p = 0.0108 4.0 3.0 2.0 1.0 0.0 20 40 60 80 100 120 140 160 180 200 Recipient eGFR (mL/min/1.73 m ) 2022 (N = 637) JHLT. 2022 Oct; 41(10): 1335-1375

  38. Multivariable Cox Analyses Mortality within 5 Years Conditional on Survival to 1 Year 2022 JHLT. 2022 Oct; 41(10): 1335-1375

  39. Pediatric Lung and Heart-Lung Recipients with PVD (1987-6/2013) Statistically Significant Categorical Risk Factors For 5-Year Mortality Conditional on 1-Year Survival with 95% Confidence Limits 2022 (N = 411) JHLT. 2022 Oct; 41(10): 1335-1375

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